{"id":12334,"date":"2026-06-02T12:17:16","date_gmt":"2026-06-02T10:17:16","guid":{"rendered":"https:\/\/crcm-marseille.fr\/uncategorized\/cdk1-phosphorylation-switches-slx4-sap-from-dna-binding-to-mus81-binding\/"},"modified":"2026-06-02T12:56:01","modified_gmt":"2026-06-02T10:56:01","slug":"cdk1-phosphorylation-switches-slx4-sap-from-dna-binding-to-mus81-binding","status":"publish","type":"post","link":"https:\/\/crcm-marseille.fr\/en\/gaillard-team\/cdk1-phosphorylation-switches-slx4-sap-from-dna-binding-to-mus81-binding\/","title":{"rendered":"CDK1 phosphorylation switches SLX4 SAP from DNA binding to MUS81 binding"},"content":{"rendered":"\n<p>SLX4 is a scaffold protein pivotal in genome protection mechanisms ranging from homologous recombination and interstrand cross-link (ICL) repair to mechanisms that deal with challenged DNA replication. Many of human SLX4 functions rely on its ability to interact and control the XPF-ERCC1, MUS81-EME1, and SLX1 structure-specific endonucleases. <\/p>\n\n\n\n<p>Interaction with MUS81 relies on the conserved SAP domain of SLX4. Since the same domain in yeast Slx4 orthologs does not interact with Mus81, we investigated whether human SLX4 SAP might have retained some ancestral MUS81-independent functions. <\/p>\n\n\n\n<p>We show that human SLX4 SAP binds DNA with a preference for branched structures such as Holliday junctions. We further discovered that phosphorylation of SLX4 SAP by CDK1, which promotes interaction with MUS81, inhibits DNA binding. <\/p>\n\n\n\n<p>We identified separation of function mutants that impair either DNA or MUS81 binding. Binding to MUS81 is required in response to ICL-inducing agents, methyl methanesulfonate (MMS), TOP1, and PARP inhibition. Instead, DNA binding is required in response to ICL-inducing agents and MMS but not after TOP1 or PARP inhibition.  <\/p>\n\n\n\n<p>Our work indicates that phosphorylation by CDK1 acts as a regulatory switch between DNA binding and MUS81-dependent functions of SLX4, to accommodate specific DNA lesions or secondary structures.<\/p>\n\n\n\n<div style=\"height:40px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"466\" src=\"https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-1024x466.webp\" alt=\"\" class=\"wp-image-12327\" srcset=\"https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-1024x466.webp 1024w, https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-300x136.webp 300w, https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-768x349.webp 768w, https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-150x68.webp 150w, https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-480x218.webp 480w\" sizes=\"auto, (max-width:767px) 480px, (max-width:1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p><em>CDK1 phosphorylation switches SLX4 SAP from DNA binding to MUS81 binding.<\/em><\/p>\n\n\n\n<h5 class=\"wp-block-heading\"><strong>Read more : Sarah Scaglione, Pierre-Henri Gaillard, Phosphorylation by CDK1 switches the function of the human SLX4 SAP domain from DNA binding to MUS81 binding,\u00a0<em>Nucleic Acids Research<\/em>, Volume 54, Issue 9, 22 May 2026, gkag442,\u00a0<a href=\"https:\/\/doi.org\/10.1093\/nar\/gkag442\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/doi.org\/10.1093\/nar\/gkag442<\/a><\/strong><br><br><br><br><\/h5>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Scaglione and Gaillard show that the SLX4 SAP domain selectively binds four-way branched DNA structures. Their findings identify CDK1 phosphorylation as a molecular switch that inhibits DNA binding while promoting MUS81 interaction, thereby temporally controlling distinct SAP functions. <\/p>\n","protected":false},"author":2,"featured_media":12326,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_tec_requires_first_save":true,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false,"_tribe_blocks_recurrence_rules":"","_tribe_blocks_recurrence_description":"","_tribe_blocks_recurrence_exclusions":"","footnotes":""},"categories":[200,201,205],"tags":[],"class_list":["post-12334","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-genome-integrity-department","category-gaillard-team","category-crcm-articles"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>CDK1 phosphorylation switches SLX4 SAP from DNA binding to MUS81 binding | CRCM<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/crcm-marseille.fr\/en\/gaillard-team\/cdk1-phosphorylation-switches-slx4-sap-from-dna-binding-to-mus81-binding\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"CDK1 phosphorylation switches SLX4 SAP from DNA binding to MUS81 binding | CRCM\" \/>\n<meta property=\"og:description\" content=\"Scaglione and Gaillard show that the SLX4 SAP domain selectively binds four-way branched DNA structures. Their findings identify CDK1 phosphorylation as a molecular switch that inhibits DNA binding while promoting MUS81 interaction, thereby temporally controlling distinct SAP functions.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/crcm-marseille.fr\/en\/gaillard-team\/cdk1-phosphorylation-switches-slx4-sap-from-dna-binding-to-mus81-binding\/\" \/>\n<meta property=\"og:site_name\" content=\"CRCM\" \/>\n<meta property=\"article:published_time\" content=\"2026-06-02T10:17:16+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-06-02T10:56:01+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/crcm-marseille.fr\/wp-content\/uploads\/2026\/06\/PH-Gaillard-news-vignette.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"333\" \/>\n\t<meta property=\"og:image:height\" content=\"198\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"author\" content=\"Delphine\" \/>\n<meta name=\"twitter:card\" 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